(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6804 - 6804

Опубликована: Июнь 20, 2024

NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative epilepsy, traumatic brain injury, substance abuse disorder (SUD), major depressive (MDD). (S)-ketamine was the first of a novel class antidepressants, rapid-acting to be approved medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development treatment-resistant depression (TRD). compound has demonstrated efficacy multiple animal models. Two clinical studies disclosed TRD bipolar depression. A study by drug sponsor recently failed reach priori endpoints but post hoc analysis revealed efficacy. value supported experimental data humans rodents, showing that it less sedating, does not produce marked psychotomimetic or dissociative effects, than (S)-ketamine, produces models range disorders. mechanisms action antidepressant effects are hypothesized due antagonism and/or non-NMDA mechanisms. We suggest further experimentation with will create improved medicines some disorders underserved current medications.

Язык: Английский

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Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions

Journal of Anesthesia and Translational Medicine, Год журнала: 2024, Номер 3(3), С. 65 - 75

Опубликована: Июль 11, 2024

Ketamine, a dissociative anesthetic, is widely utilized in both human and veterinary anesthesia. Its (S)-enantiomer, esketamine, similarly employed for anesthesia analgesia. The anesthetic effects of ketamine esketamine arise from their antagonism the N-methyl-D-aspartate receptor (NMDAR). In field psychiatry, rapid-acting antidepressant properties severe depression have generated significant interest, resulting its increased off-label usage United States (U.S.). 2019, nasal spray received approval use U.S. Europe. However, concerns emerged regarding potential adverse effects, including long-term efficacy, addiction risks, suicide risk clinical settings. contrast, arketamine, (R)-enantiomer ketamine, exhibits superior longer-lasting rodent models depression, with fewer side compared to esketamine. Nevertheless, research on efficacy safety arketamine patients remains limited. This article provides concise exploration historical two enantiomers while also delving into future directions application these fields.

Язык: Английский

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Depression-like phenotypes in mice following common bile duct ligation: Insights into the gut–liver–brain axis via the vagus nerve

Neurobiology of Disease, Год журнала: 2024, Номер 192, С. 106433 - 106433

Опубликована: Фев. 7, 2024

Depression frequently occurs in patients with liver cirrhosis, yet the reasons for this correlation are not fully understood. Dysbiosis of gut microbiota has been implicated depression through gut–brain axis via vagus nerve. This study explored potential role gut–liver–brain nerve depression-like phenotypes mice cirrhosis. These underwent common bile duct ligation (CBDL), a method used to stimulate To assess behaviors, behavioral tests were conducted 10 days following either sham or CBDL surgeries. The displayed symptoms such as splenomegaly, elevated plasma levels interleukin-6 and tumor necrosis factor-α, decreased synaptic proteins prefrontal cortex (PFC), disrupted balance, changes blood metabolites (or lipids). Additionally, there positive negative correlations between relative abundance microbiome data Significantly, these reversed by performing subdiaphragmatic vagotomy. Intriguingly, improved after single injection arketamine, new antidepressant. results suggest that CBDL-induced mediated nerve, arketamine might offer treatment approach cirrhosis patients.

Язык: Английский

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Psychedelic therapy in depression and substance use disorders

European Journal of Neuroscience, Год журнала: 2024, Номер 60(2), С. 4063 - 4077

Опубликована: Май 21, 2024

Abstract Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals different cultures thousands years. Classical psychedelics N,N′‐dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations perception, emotion cognition by acting through serotonin 5‐HT 2A receptor activation. Lysergic acid diethylamide, first famous breakthrough field, was discovered chance Albert Hoffman Zurich Sandoz laboratory 1943, studies on its psychoactive effects began to take place literature. Studies this area were blocked after legislation controlling use research psychedelic drugs came into force 1967, but since 1990s, it has started be matter scientific curiosity again groups. In particular, with crucial reports psychotherapy‐assisted psilocybin applications life‐threatening cancer‐related anxiety depression, new avenues opened treatment psychiatric diseases such as treatment‐resistant depression substance addictions. An increasing number show that very promising potential neuropsychiatric where desired efficiency cannot achieved conventional methods. context, we discuss therapy, encompassing historical development, therapeutic effects—especially trauma disorders disorders—within framework ethical considerations.

Язык: Английский

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The vagus nerve: An old but new player in brain–body communication

Brain Behavior and Immunity, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Is there a risk of esketamine misuse in clinical practice?

Therapeutic Advances in Drug Safety, Год журнала: 2025, Номер 16

Опубликована: Янв. 1, 2025

In 2019, intranasal esketamine gained approval as a promising therapy for those individuals grappling with treatment-resistant depression. Both clinical trials and real-world studies have underscored its efficacy in alleviating remitting depressive symptoms, sustained benefits observed nearly 4.5 years. As the S-enantiomer of ketamine, esketamine's dosing guidelines strict medical supervision stem from prior research on ketamine's use depression history recreational drug. Despite initial concerns, long-term not documented instances abuse, misuse, addiction or withdrawal, same was found case reports subsamples high-risk populations comorbidities such substance disorder alcohol disorder. Esketamine has proven to be safe well tolerated without fostering new-onset vulnerable groups. Real-world reinforced these observations, reporting no adverse events (AEs) related pharmacological interactions any other substance, drug craving, misuse diversion use. Reports craving remain rare, only one report 2022. Most drug-related AEs reported pharmacovigilance databases are identified product's technical data sheet known frequency. More importantly, register illicit acquisition tampering obtaining ketamine altered products our search. Overall, review confirms safety across diverse patient populations, reassuring responsible scarcity abuse since introduction market.

Язык: Английский

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Efficacy and safety of esketamine for perioperative depression in patients undergoing elective surgery: A meta-analysis of randomized controlled trials

Asian Journal of Psychiatry, Год журнала: 2024, Номер 95, С. 103997 - 103997

Опубликована: Март 11, 2024

Язык: Английский

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Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis

Neurobiology of Disease, Год журнала: 2024, Номер 199, С. 106573 - 106573

Опубликована: Июнь 18, 2024

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors chronic social defeat stress (CSDS) model depression. This study investigated whether spleen contributes arketamine CSDS model. We found that splenectomy significantly inhibited arketamine's CSDS-susceptible mice. RNA-sequencing analysis identified oxidative phosphorylation (OXPHOS) pathway prefrontal cortex (PFC) as a key mediator splenectomy's impact on effects. Furthermore, oligomycin A, an inhibitor OXPHOS pathway, reversed suppressive Specific genes within pathways, such COX11, UQCR11 ATP5e, may contribute these inhibitory Notably, transforming growth factor (TGF)-β1, along with appears modulate Additionally, SRI-01138, agonist TGF-β1 receptor, alleviated Subdiaphragmatic vagotomy also counteracted These findings suggest PFC play significant roles arketamine, mediated through spleen-brain axis via vagus nerve.

Язык: Английский

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Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-β1

Journal of Affective Disorders, Год журнала: 2024, Номер 367, С. 745 - 755

Опубликована: Сен. 3, 2024

Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, relationship between these remains unclear. Arketamine, (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects CRS-exposed mice. We examined whether arketamine can improve both brains Additionally, we investigated role transforming growth factor β1 (TGF-β1) beneficial arketamine. A single dose (10 mg/kg) improved behavior corpus callosum Correlations were found this region. Furthermore, pretreatment with RepSox, an inhibitor TGF-β1 receptor, significantly blocked on Finally, a intranasal administration ameliorated The precise mechanisms by which contributes to remain These data suggest that CRS-induced may contribute behaviors, mitigate changes through TGF-β1-dependent mechanism.

Язык: Английский

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Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice

European Journal of Pharmacology, Год журнала: 2024, Номер 985, С. 177096 - 177096

Опубликована: Ноя. 3, 2024

The novel antidepressant arketamine, the (R)-enantiomer of ketamine, has been shown to ameliorate demyelination and facilitate remyelination in brains cuprizone (CPZ)-treated mice. However, mechanisms behind its effects remain unclear. Given role transforming growth factor β1 (TGF-β1) arketamine's antidepressant-like effects, we examined whether TGF-β1 also plays a on CPZ-treated Additionally, investigated intranasal these Repeated intermittent administration arketamine (10 mg/kg/day, twice weekly for last 2-weeks) attenuated corpus callosum (CC) CPZ (6 weeks)-treated Furthermore, pretreatment with RepSox mg/kg/day), an inhibitor TGF-β receptor 1, significantly blocked beneficial CC repeated (3.0 μg/kg/day, 2 weeks) ameliorated facilitated These data suggest that can mitigate facilitates mice through TGF-β1-dependent mechanism.

Язык: Английский

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